SAN ANTONIO—Adding fulvestrant (Faslodex) to anastrozole (Arimidex) therapy had “not a hint of an effect” for first relapse in hormone receptor-positive breast cancer, according to Jonas Bergh, MD, an investigator in the FACT trial. The open-label, phase III study looked at the loading dose of fulvestrant combined with anastrozole compared with anastrozole alone in 514 patients.

Fulvestrant is usually given at 250 mg/mo, which results in a pharmacokinetic steady state after three to six months, Dr. Bergh said. The more aggressive loading schedule used in this study—500 mg on day zero, 250 mg on days 14 and 28, and 250 mg once a month thereafter plus 1 mg anastrazole daily—offered a pharmacokinetic steady state at 28 days.

“We had two major prerequisites that made us optimistic,” he said. “We had a better loading schedule, which should have given us better pharmacokinetic concentration right away at the start of therapy, and we had two nice preclinical studies demonstrating a clear benefit of combined use” (J Clin Oncol 26:1664-1670, 2008; Cancer Res 68:3516-3522, 2008).

Patients were randomized to fulvestrant plus anastrazole at the study dosage or to anastrozole alone (1 mg daily). The median patient age was 65 in the combination arm and 63 in the anastrozole arm (SABCS 2009 abstract 23).

With regard to previous adjuvant endocrine therapy, “30% in the combined arm and 35% in the anastrazole arm received no prior adjuvant endocrine therapy,” Dr. Bergh said. “That was quite a big surprise to me. Twelve percent and 14%, respectively, had a relapse within two years of completion of tamoxifen. Twenty-eight percent and 25%, respectively, had relapse more than two years after completion of tamoxifen. Twenty-seven percent in the combined arm and 24% in the anastrozole-alone arm relapsed on tamoxifen therapy. Only five individuals who had previous aromatase inhibitor therapy were included.”

He added that “these patients should have been endrocine-responsive because three-fourths of the patients were both estrogen receptor-positive and progesterone receptor-positive. Only five individuals were ER-negative and PgR-positive.”

The primary endpoint for the study was time to progression (TTP); secondary endpoints included objective response rate (ORR) and clinical benefit rate (CBR).

The median TTP was 10.2 months for the anastrozole-only arm and 10.8 months for the combination arm (P = .91). Dr. Bergh reported that disease progression was demonstrated in 77.5% of the combination arm and 78.1% of the single-agent arm. The investigator-assessed ORR on patients with measurable disease for the combination arm was 31.8% vs 33.6% for the anastrozole arm. The CBR rate for the fulvestrant plus anastrozole arm was 55% vs 51% for the single-agent arm.

There were more instances of liver metastases in the combination arm than in the single-agent arm, Dr. Bergh said. More patients in the combination arm experienced hot flashes.

In terms of overall survival, 102 patients died in each arm. There were three cases of cardiac failure in the combination arm, but the instances of cardiac failure were result was not statistically significant. However, the median survival at 38 months was good, especially for metastatic breast cancer patients, he said.